A Discussion of Mitochondrially Derived Peptide MOTS-c

A number of mitochondrially derived peptides are thought to have positive effects on cell function, though as for most of the approaches of this nature, it is unclear that it is any better than a structured exercise program. One of the better studied of these peptides is MOTS-c, which is itself upregulated by exercise - arguably one of a number of known exercise mimetics. Delivering signal molecules that are normally upregulated by exercise should in principle recapture some of the beneficial effects of exercise, but so far this line of development has yet to much improve on exercise itself.

Mitochondria are organelles required for the production of ATP. A mitochondrion exhibits semi-autonomous genetic systems, independent genomes, and unique genetic codes that are similar to those found in bacteria. Recently, a short open reading frame (sORF) encoded in the mitochondrial genome has been discovered. These sORF produce bioactive peptides, collectively known as mitochondrial-derived peptides (MDP), which have a wide range of physiological functions and can explain how mitochondria communicate within and between cells in a specific disease environment. Mitochondrial-derived peptides may answer the key biological problems that have plagued the field for decades (such as mitochondrial-nuclear communication, metabolic dysfunction, etc.). Whether in the form of mitochondrial-derived peptide itself or in terms of sORF, mitochondrial-derived peptide is suitable for research as a therapeutic agent.

Mitochondrial-derived peptide called MOTS-c has been shown to significantly reduce the level of pro-inflammatory factors in mice and increase anti-inflammatory factors and insulin-stimulated glucose treatment rates, as well as glucose homeostasis. Furthermore, human studies showed that exercise increased MOTS-c levels in skeletal muscle and blood circulation, indicating that MOTS-c is a mitochondrial-derived peptide induced by skeletal muscle exercise. Additionally, studies have revealed the importance of MOTS-c in regulating obesity and diabetes, longevity, and cardiovascular disease. Specifically, this paper discusses the application of mitochondrial-derived peptides, including MOTS-c, in the treatment of diseases and anticipates the future development direction of MOTS-c combining synthetic biology to provide new ideas on how it can be developed and applied.

Link: https://doi.org/10.3389/fendo.2023.1120533

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